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Reactive antibodies against bacillus Calmette‐Guerin heat‐shock protein‐65 potentially predict the outcome of immunotherapy for high‐grade transitional cell carcinoma of the bladder
Author(s) -
Ardelt Peter U.,
Kneitz Burkhard,
Adam Patrick,
Reiss Cora,
Kocot Arkadius,
Fensterle Joachim,
Chen Limor,
Pasqualini Renata,
Arap Wadih,
Gerharz Elmar W.,
Riedmiller Hubertus
Publication year - 2009
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.24770
Subject(s) - medicine , immunotherapy , bladder cancer , transitional cell carcinoma , mycobacterium bovis , immunology , epitope , antibody , heat shock protein , bcg vaccine , oncology , immune system , carcinoma in situ , cystectomy , cancer , antigen , pathology , vaccination , biology , tuberculosis , mycobacterium tuberculosis , biochemistry , gene
BACKGROUND: Intravesical immunotherapy with Mycobacterium bovis ( M. bovis ) bacillus Calmette‐Guerin (BCG) is the current standard of care against superficial, high‐grade transitional cell carcinoma (TCC) of the urinary bladder (carcinoma in situ and pathologic T1, grade 3 disease). However, individual patient outcome is barely predictable because of the lack of serum markers. Consequently, progression to muscle‐invasive bladder cancer and critical delay of treatments (such as neoadjuvant combination chemotherapy and/or radical cystectomy) often occur. The objectives of this study were to identify a marker for measuring the BCG‐induced immune response and to predict the outcomes and potential improvements of BCG immunotherapy. METHODS: Because host immunoresponse mediates BCG activity, the authors screened a combinatorial random peptide library on the circulating pool of immunoglobulins (Igs) purified from an index patient after successful BCG immunotherapy to identify the corresponding target antigen(s). RESULTS: An immunogenic peptide motif was selected, isolated, and validated from M. bovis BCG heat‐shock protein 65 (HSP‐65) as a dominant epitope of the humoral response to treatment. Increasing IgA and IgG anti‐HSP‐65 titers specifically predicted a positive patient outcome in a cohort of patients with bladder cancer relative to several cohorts of control patients. CONCLUSIONS: The current results indicated that antibody production against M. bovis BCG HSP‐65 can serve as a serologic marker for the predictive outcome of BCG immunotherapy. Subsequent studies will determine the value of this candidate marker to modify BCG‐based treatment for individual patients with bladder cancer. Cancer 2010. © 2009 American Cancer Society.